The overall objective of this project is to employ the transgenic mouse system i study neoplastic development in vivo. This system provides a new way of investigating tissue-specific and developmental stage-specific regulation of both natural and manipulated gene sequences introduced into the germ line of an animal. We are currently focusing on the neoplastic development in the liver employing the v-raf oncogene as the transforming agent. The v-raf under the control of liver-specific promoters from both albumin and alpha-fetoprotein gene has been microinjected into the I-cell embryo, and we are in the process of establishing transgenic lines from the progeny.